Despite the promise and excitement of gene therapy, it is still a long way from practice. Two major problems hindering gene therapy are that (1) gene transfers to non-dividing cells are still extremely inefficient, and (2) gene transfer to specific desired non-dividing cells within a population of other cell types is even more inefficient. Thus, any way to increase the amount of gene transfer will greatly benefit this emerging field.
Many techniques and vectors for gene therapy have been developed to target genes to cells, including replication-deficient recombinant retroviruses, adenoviruses, and adeno-associated viruses, as well as non-viral vectors such as ligand-DNA conjugates or DNA lipofection. However, most targeting techniques developed to date have only addressed the ability to internalize the DNA into the cytoplasm of the cell. It is clear that gene therapy relies on the ability of targeted genes to enter the nucleus. This is true regardless of how the DNA or RNA is targeted to the cell; once within the cytoplasm, the gene must become nuclear to be transcribed, replicated, and maintained either in an integrated or episomal state, yet there has been little attention directed toward either discovering or exploiting the mechanisms used by the cell to direct DNA to the nucleus.
The promise and potential of gene therapy techniques to cure or to alleviate symptoms in a multitude of disorders and diseases results in a continuing need for ways to increase the amount of gene transfer to cells. Ideally, a way to increase the amount of gene transfer to the nucleus of a specific cell type would exist for cell-specific targeting of gene therapy.